UV irradiation inhibits ABC transporters via generation of ADP-ribose by concerted action of poly(ADP-ribose) polymerase-1 and glycohydrolase

被引:26
作者
Dumitriu, IE [1 ]
Voll, RE [1 ]
Kolowos, W [1 ]
Gaipl, US [1 ]
Heyder, P [1 ]
Kalden, JR [1 ]
Herrmann, M [1 ]
机构
[1] Univ Erlangen Nurnberg, Inst Clin Immunol, Dept Internal Med 3, D-91054 Erlangen, Germany
关键词
ABC transporters; PARP-1; PARP-null cells; PARG;
D O I
10.1038/sj.cdd.4401348
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
ATP-binding cassette (ABC) transporters are involved in the transport of multiple substrates across cellular membranes, including metabolites, proteins, and drugs. Employing a functional fluorochrome export assay, we found that UVB irradiation strongly inhibits the activity of ABC transporters. Specific inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) restored the function of ABC transporters in UVB-irradiated cells, and PARP-1-deficient cells did not undergo UVB-induced membrane transport inhibition. These data suggest that PARP-1 activation is necessary for ABC transporter functional downregulation. The hydrolysis of poly(ADP-ribose) by poly(ADP-ribose) glycohydrolase (PARG) was also required, since specific PARG inhibitors, which limit the production of ADP-ribose molecules, restored the function of ABC transporters. Furthermore, ADP-ribose molecules potently inhibited the activity of the ABC transporter P-glycoprotein. Hence, poly(ADP-ribose) metabolism appears to play a novel role in the regulation of ABC transporters.
引用
收藏
页码:314 / 320
页数:7
相关论文
共 41 条
[1]   POLY(ADP-RIBOSE) CATABOLISM IN MAMMALIAN-CELLS EXPOSED TO DNA-DAMAGING AGENTS [J].
ALVAREZGONZALEZ, R ;
ALTHAUS, FR .
MUTATION RESEARCH, 1989, 218 (02) :67-74
[2]   The secretory route of the leaderless protein interleukin 1β involves exocytosis of endolysosome-related vesicles [J].
Andrei, C ;
Dazzi, C ;
Lotti, L ;
Torrisi, MR ;
Chimini, G ;
Rubartelli, A .
MOLECULAR BIOLOGY OF THE CELL, 1999, 10 (05) :1463-1475
[3]   Inhibition of nitric oxide synthase ameliorates cellular injury in sickle cell mouse kidneys [J].
Bank, N ;
Kiroycheva, M ;
Singhal, PC ;
Anthony, GM ;
Southan, GJ ;
Szabo, C .
KIDNEY INTERNATIONAL, 2000, 58 (01) :82-89
[4]   Comparative effects of Bcl-2 over-expression and ZVAD.FMK treatment on dexamethasone and VP16-induced apoptosis in CEM cells [J].
Benson, RSP ;
Dive, C ;
Watson, AJM .
CELL DEATH AND DIFFERENTIATION, 1998, 5 (05) :432-439
[5]   CXCR4 and CD4 mediate a rapid CD95-independent cell death in CD4+ T cells [J].
Berndt, C ;
Möpps, B ;
Angermüller, S ;
Gierschik, P ;
Krammer, PH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (21) :12556-12561
[6]   Specific docking of apolipoprotein A-I at the cell surface requires a functional ABCA1 transporter [J].
Chambenoit, O ;
Hamon, Y ;
Marguet, D ;
Rigneault, H ;
Rosseneu, M ;
Chimini, G .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (13) :9955-9960
[7]   INTERNAL DUPLICATION AND HOMOLOGY WITH BACTERIAL TRANSPORT PROTEINS IN THE MDR1 (P-GLYCOPROTEIN) GENE FROM MULTIDRUG-RESISTANT HUMAN-CELLS [J].
CHEN, CJ ;
CHIN, JE ;
UEDA, K ;
CLARK, DP ;
PASTAN, I ;
GOTTESMAN, MM ;
RONINSON, IB .
CELL, 1986, 47 (03) :381-389
[8]   OVEREXPRESSION OF A TRANSPORTER GENE IN A MULTIDRUG-RESISTANT HUMAN LUNG-CANCER CELL-LINE [J].
COLE, SPC ;
BHARDWAJ, G ;
GERLACH, JH ;
MACKIE, JE ;
GRANT, CE ;
ALMQUIST, KC ;
STEWART, AJ ;
KURZ, EU ;
DUNCAN, AMV ;
DEELEY, RG .
SCIENCE, 1992, 258 (5088) :1650-1654
[9]   Importance of poly(ADP-ribose) glycohydrolase in the control of poly(ADP-ribose) metabolism [J].
Davidovic, L ;
Vodenicharov, M ;
Affar, EB ;
Poirier, GG .
EXPERIMENTAL CELL RESEARCH, 2001, 268 (01) :7-13
[10]  
Dean M, 2001, J LIPID RES, V42, P1007